JP2022523596A - 結腸直腸進行新生物、進行腺腫、及び/又は結腸直腸癌をスクリーニング、診断、及び/又はモニタリングする改善された方法 - Google Patents
結腸直腸進行新生物、進行腺腫、及び/又は結腸直腸癌をスクリーニング、診断、及び/又はモニタリングする改善された方法 Download PDFInfo
- Publication number
- JP2022523596A JP2022523596A JP2021553792A JP2021553792A JP2022523596A JP 2022523596 A JP2022523596 A JP 2022523596A JP 2021553792 A JP2021553792 A JP 2021553792A JP 2021553792 A JP2021553792 A JP 2021553792A JP 2022523596 A JP2022523596 A JP 2022523596A
- Authority
- JP
- Japan
- Prior art keywords
- crc
- seq
- subject
- advanced
- screening
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 200
- 208000003200 Adenoma Diseases 0.000 title claims abstract description 110
- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 89
- 238000012216 screening Methods 0.000 title claims abstract description 87
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 84
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims abstract description 76
- 238000012544 monitoring process Methods 0.000 title claims abstract description 31
- 230000001580 bacterial effect Effects 0.000 claims abstract description 81
- 230000002550 fecal effect Effects 0.000 claims abstract description 68
- 206010001233 Adenoma benign Diseases 0.000 claims abstract description 63
- 208000035269 cancer or benign tumor Diseases 0.000 claims abstract description 14
- 238000009534 blood test Methods 0.000 claims abstract description 13
- 108091034117 Oligonucleotide Proteins 0.000 claims description 88
- 238000012360 testing method Methods 0.000 claims description 84
- 241000684246 Peptostreptococcus stomatis Species 0.000 claims description 69
- 241000606124 Bacteroides fragilis Species 0.000 claims description 66
- 241000606123 Bacteroides thetaiotaomicron Species 0.000 claims description 52
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 45
- 238000011002 quantification Methods 0.000 claims description 33
- 239000003550 marker Substances 0.000 claims description 30
- 241000894006 Bacteria Species 0.000 claims description 24
- 241001112695 Clostridiales Species 0.000 claims description 19
- 210000004369 blood Anatomy 0.000 claims description 19
- 239000008280 blood Substances 0.000 claims description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims description 17
- 102000001554 Hemoglobins Human genes 0.000 claims description 14
- 108010054147 Hemoglobins Proteins 0.000 claims description 14
- 230000000984 immunochemical effect Effects 0.000 claims description 13
- 241001608234 Faecalibacterium Species 0.000 claims description 11
- 241000588724 Escherichia coli Species 0.000 claims description 8
- 241000193789 Gemella Species 0.000 claims description 8
- 241001464956 Collinsella Species 0.000 claims description 5
- 238000011529 RT qPCR Methods 0.000 claims description 2
- 238000002052 colonoscopy Methods 0.000 abstract description 52
- 230000001965 increasing effect Effects 0.000 abstract description 21
- 239000002246 antineoplastic agent Substances 0.000 abstract description 16
- 229940124597 therapeutic agent Drugs 0.000 abstract description 10
- 238000010586 diagram Methods 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 90
- 201000011510 cancer Diseases 0.000 description 48
- 241001147749 Gemella morbillorum Species 0.000 description 35
- 238000001514 detection method Methods 0.000 description 31
- 239000000090 biomarker Substances 0.000 description 27
- 230000035945 sensitivity Effects 0.000 description 24
- 238000003745 diagnosis Methods 0.000 description 20
- 108020004414 DNA Proteins 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 244000005709 gut microbiome Species 0.000 description 16
- 150000007523 nucleic acids Chemical group 0.000 description 16
- 238000003752 polymerase chain reaction Methods 0.000 description 16
- 241000606125 Bacteroides Species 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 238000009396 hybridization Methods 0.000 description 15
- 230000000968 intestinal effect Effects 0.000 description 14
- 239000002773 nucleotide Substances 0.000 description 13
- 238000003753 real-time PCR Methods 0.000 description 13
- 241001330547 Collinsella intestinalis Species 0.000 description 12
- 241000398180 Roseburia intestinalis Species 0.000 description 12
- 230000003321 amplification Effects 0.000 description 12
- -1 and v. Optionally Polymers 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 230000000875 corresponding effect Effects 0.000 description 12
- 238000003199 nucleic acid amplification method Methods 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 210000001072 colon Anatomy 0.000 description 11
- 210000003608 fece Anatomy 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 11
- 238000003556 assay Methods 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000002591 computed tomography Methods 0.000 description 10
- 230000003902 lesion Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 8
- 208000037062 Polyps Diseases 0.000 description 8
- 238000009541 flexible sigmoidoscopy Methods 0.000 description 8
- 210000001035 gastrointestinal tract Anatomy 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 230000001613 neoplastic effect Effects 0.000 description 8
- 210000000664 rectum Anatomy 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 7
- 241000736262 Microbiota Species 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 230000000112 colonic effect Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 108020004465 16S ribosomal RNA Proteins 0.000 description 6
- 208000004804 Adenomatous Polyps Diseases 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 206010058314 Dysplasia Diseases 0.000 description 6
- 208000009956 adenocarcinoma Diseases 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000004422 calculation algorithm Methods 0.000 description 6
- 229940127089 cytotoxic agent Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000001839 endoscopy Methods 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 238000007400 DNA extraction Methods 0.000 description 5
- 241000792859 Enema Species 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 229910052788 barium Inorganic materials 0.000 description 5
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 5
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 239000007920 enema Substances 0.000 description 5
- 229940095399 enema Drugs 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 5
- 230000000813 microbial effect Effects 0.000 description 5
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 5
- 230000004580 weight loss Effects 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- 241001662466 Coriobacteriia Species 0.000 description 4
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 4
- 102000001301 EGF receptor Human genes 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- 241000147041 Guaiacum officinale Species 0.000 description 4
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 241000191992 Peptostreptococcus Species 0.000 description 4
- 206010038063 Rectal haemorrhage Diseases 0.000 description 4
- 238000004590 computer program Methods 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000012295 fluorescence in situ hybridization assay Methods 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- 239000003966 growth inhibitor Substances 0.000 description 4
- 229940091561 guaiac Drugs 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 238000007481 next generation sequencing Methods 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 230000000391 smoking effect Effects 0.000 description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 4
- 239000003053 toxin Substances 0.000 description 4
- 231100000765 toxin Toxicity 0.000 description 4
- 108700012359 toxins Proteins 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
- 208000004998 Abdominal Pain Diseases 0.000 description 3
- 241000193833 Bacillales Species 0.000 description 3
- 241001112696 Clostridia Species 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 3
- 108060006698 EGF receptor Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 201000006107 Familial adenomatous polyposis Diseases 0.000 description 3
- 208000017095 Hereditary nonpolyposis colon cancer Diseases 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 description 3
- 230000018199 S phase Effects 0.000 description 3
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 229930003268 Vitamin C Natural products 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 3
- 201000002758 colorectal adenoma Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
- 238000003935 denaturing gradient gel electrophoresis Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 235000008191 folinic acid Nutrition 0.000 description 3
- 239000011672 folinic acid Substances 0.000 description 3
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229960004768 irinotecan Drugs 0.000 description 3
- 235000020997 lean meat Nutrition 0.000 description 3
- 229960001691 leucovorin Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 102000042567 non-coding RNA Human genes 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 244000039328 opportunistic pathogen Species 0.000 description 3
- 229960001756 oxaliplatin Drugs 0.000 description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 102000013415 peroxidase activity proteins Human genes 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 206010038038 rectal cancer Diseases 0.000 description 3
- 201000001275 rectum cancer Diseases 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000002689 soil Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- 229960003048 vinblastine Drugs 0.000 description 3
- 239000011718 vitamin C Substances 0.000 description 3
- 235000019154 vitamin C Nutrition 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 2
- 241001156002 Anthonomus pomorum Species 0.000 description 2
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
- 241001464948 Coprococcus Species 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 208000027244 Dysbiosis Diseases 0.000 description 2
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 2
- 241000605980 Faecalibacterium prausnitzii Species 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 208000008051 Hereditary Nonpolyposis Colorectal Neoplasms Diseases 0.000 description 2
- 101001051777 Homo sapiens Protein kinase C alpha type Proteins 0.000 description 2
- 108010000521 Human Growth Hormone Proteins 0.000 description 2
- 102000002265 Human Growth Hormone Human genes 0.000 description 2
- 239000000854 Human Growth Hormone Substances 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 201000005027 Lynch syndrome Diseases 0.000 description 2
- 230000027311 M phase Effects 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 206010033307 Overweight Diseases 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108010006785 Taq Polymerase Proteins 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 2
- 238000011319 anticancer therapy Methods 0.000 description 2
- 239000013059 antihormonal agent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 238000010170 biological method Methods 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 description 2
- PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229960000684 cytarabine Drugs 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 229960003901 dacarbazine Drugs 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000013872 defecation Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000003748 differential diagnosis Methods 0.000 description 2
- 230000007140 dysbiosis Effects 0.000 description 2
- 238000007848 endpoint PCR Methods 0.000 description 2
- 229960001904 epirubicin Drugs 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000012041 food component Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- CHPZKNULDCNCBW-UHFFFAOYSA-N gallium nitrate Chemical compound [Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O CHPZKNULDCNCBW-UHFFFAOYSA-N 0.000 description 2
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 102000018146 globin Human genes 0.000 description 2
- 108060003196 globin Proteins 0.000 description 2
- 230000002414 glycolytic effect Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 150000003278 haem Chemical class 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 206010022694 intestinal perforation Diseases 0.000 description 2
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- 238000010801 machine learning Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229960001428 mercaptopurine Drugs 0.000 description 2
- 238000010197 meta-analysis Methods 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000012175 pyrosequencing Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- 238000002579 sigmoidoscopy Methods 0.000 description 2
- 230000005586 smoking cessation Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960001196 thiotepa Drugs 0.000 description 2
- 238000007671 third-generation sequencing Methods 0.000 description 2
- 229960003087 tioguanine Drugs 0.000 description 2
- 229960000303 topotecan Drugs 0.000 description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 2
- 241001300301 uncultured bacterium Species 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- YXTKHLHCVFUPPT-YYFJYKOTSA-N (2s)-2-[[4-[(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid;(1r,2r)-1,2-dimethanidylcyclohexane;5-fluoro-1h-pyrimidine-2,4-dione;oxalic acid;platinum(2+) Chemical compound [Pt+2].OC(=O)C(O)=O.[CH2-][C@@H]1CCCC[C@H]1[CH2-].FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 YXTKHLHCVFUPPT-YYFJYKOTSA-N 0.000 description 1
- FLWWDYNPWOSLEO-HQVZTVAUSA-N (2s)-2-[[4-[1-(2-amino-4-oxo-1h-pteridin-6-yl)ethyl-methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1C(C)N(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FLWWDYNPWOSLEO-HQVZTVAUSA-N 0.000 description 1
- URLVCROWVOSNPT-XOTOMLERSA-N (2s)-4-[(13r)-13-hydroxy-13-[(2r,5r)-5-[(2r,5r)-5-[(1r)-1-hydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2h-furan-5-one Chemical compound O1[C@@H]([C@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCCCCC=2C(O[C@@H](C)C=2)=O)CC1 URLVCROWVOSNPT-XOTOMLERSA-N 0.000 description 1
- LDLGBNXSBZFATB-BYPYZUCNSA-N (2s)-5-amino-2-(difluoromethylamino)pentanoic acid Chemical compound NCCC[C@@H](C(O)=O)NC(F)F LDLGBNXSBZFATB-BYPYZUCNSA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- TVIRNGFXQVMMGB-OFWIHYRESA-N (3s,6r,10r,13e,16s)-16-[(2r,3r,4s)-4-chloro-3-hydroxy-4-phenylbutan-2-yl]-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H](O)[C@@H](Cl)C=2C=CC=CC=2)C/C=C/C(=O)N1 TVIRNGFXQVMMGB-OFWIHYRESA-N 0.000 description 1
- AESVUZLWRXEGEX-DKCAWCKPSA-N (7S,9R)-7-[(2S,4R,5R,6R)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione iron(3+) Chemical compound [Fe+3].COc1cccc2C(=O)c3c(O)c4C[C@@](O)(C[C@H](O[C@@H]5C[C@@H](N)[C@@H](O)[C@@H](C)O5)c4c(O)c3C(=O)c12)C(=O)CO AESVUZLWRXEGEX-DKCAWCKPSA-N 0.000 description 1
- JXVAMODRWBNUSF-KZQKBALLSA-N (7s,9r,10r)-7-[(2r,4s,5s,6s)-5-[[(2s,4as,5as,7s,9s,9ar,10ar)-2,9-dimethyl-3-oxo-4,4a,5a,6,7,9,9a,10a-octahydrodipyrano[4,2-a:4',3'-e][1,4]dioxin-7-yl]oxy]-4-(dimethylamino)-6-methyloxan-2-yl]oxy-10-[(2s,4s,5s,6s)-4-(dimethylamino)-5-hydroxy-6-methyloxan-2 Chemical compound O([C@@H]1C2=C(O)C=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C2[C@@H](O[C@@H]2O[C@@H](C)[C@@H](O[C@@H]3O[C@@H](C)[C@H]4O[C@@H]5O[C@@H](C)C(=O)C[C@@H]5O[C@H]4C3)[C@H](C2)N(C)C)C[C@]1(O)CC)[C@H]1C[C@H](N(C)C)[C@H](O)[C@H](C)O1 JXVAMODRWBNUSF-KZQKBALLSA-N 0.000 description 1
- INAUWOVKEZHHDM-PEDBPRJASA-N (7s,9s)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2r,4s,5s,6s)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCOCC1 INAUWOVKEZHHDM-PEDBPRJASA-N 0.000 description 1
- NOPNWHSMQOXAEI-PUCKCBAPSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-(2,3-dihydropyrrol-1-yl)-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)CO)CCC=C1 NOPNWHSMQOXAEI-PUCKCBAPSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- AGNGYMCLFWQVGX-AGFFZDDWSA-N (e)-1-[(2s)-2-amino-2-carboxyethoxy]-2-diazonioethenolate Chemical compound OC(=O)[C@@H](N)CO\C([O-])=C\[N+]#N AGNGYMCLFWQVGX-AGFFZDDWSA-N 0.000 description 1
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 description 1
- BOMZMNZEXMAQQW-UHFFFAOYSA-N 2,5,11-trimethyl-6h-pyrido[4,3-b]carbazol-2-ium-9-ol;acetate Chemical compound CC([O-])=O.C[N+]1=CC=C2C(C)=C(NC=3C4=CC(O)=CC=3)C4=C(C)C2=C1 BOMZMNZEXMAQQW-UHFFFAOYSA-N 0.000 description 1
- QCXJFISCRQIYID-IAEPZHFASA-N 2-amino-1-n-[(3s,6s,7r,10s,16s)-3-[(2s)-butan-2-yl]-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-10-propan-2-yl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-4,6-dimethyl-3-oxo-9-n-[(3s,6s,7r,10s,16s)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propa Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N=C2C(C(=O)N[C@@H]3C(=O)N[C@H](C(N4CCC[C@H]4C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]3C)=O)[C@@H](C)CC)=C(N)C(=O)C(C)=C2O2)C2=C(C)C=C1 QCXJFISCRQIYID-IAEPZHFASA-N 0.000 description 1
- FDAYLTPAFBGXAB-UHFFFAOYSA-N 2-chloro-n,n-bis(2-chloroethyl)ethanamine Chemical compound ClCCN(CCCl)CCCl FDAYLTPAFBGXAB-UHFFFAOYSA-N 0.000 description 1
- VNBAOSVONFJBKP-UHFFFAOYSA-N 2-chloro-n,n-bis(2-chloroethyl)propan-1-amine;hydrochloride Chemical compound Cl.CC(Cl)CN(CCCl)CCCl VNBAOSVONFJBKP-UHFFFAOYSA-N 0.000 description 1
- PWMYMKOUNYTVQN-UHFFFAOYSA-N 3-(8,8-diethyl-2-aza-8-germaspiro[4.5]decan-2-yl)-n,n-dimethylpropan-1-amine Chemical compound C1C[Ge](CC)(CC)CCC11CN(CCCN(C)C)CC1 PWMYMKOUNYTVQN-UHFFFAOYSA-N 0.000 description 1
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical class N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
- 206010000077 Abdominal mass Diseases 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 1
- QMGUSPDJTPDFSF-UHFFFAOYSA-N Aldophosphamide Chemical compound ClCCN(CCCl)P(=O)(N)OCCC=O QMGUSPDJTPDFSF-UHFFFAOYSA-N 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 108090000644 Angiozyme Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 102000014654 Aromatase Human genes 0.000 description 1
- 108010078554 Aromatase Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 1
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 1
- 108010003455 BLyS receptor Proteins 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 241000423333 Bacteroides fragilis NCTC 9343 Species 0.000 description 1
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000219193 Brassicaceae Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101100380241 Caenorhabditis elegans arx-2 gene Proteins 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
- 206010008399 Change of bowel habit Diseases 0.000 description 1
- 102100021809 Chorionic somatomammotropin hormone 1 Human genes 0.000 description 1
- 208000037384 Clostridium Infections Diseases 0.000 description 1
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 1
- 206010054236 Clostridium difficile infection Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010048832 Colon adenoma Diseases 0.000 description 1
- 208000019399 Colonic disease Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229930188224 Cryptophycin Natural products 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- AUGQEEXBDZWUJY-ZLJUKNTDSA-N Diacetoxyscirpenol Chemical compound C([C@]12[C@]3(C)[C@H](OC(C)=O)[C@@H](O)[C@H]1O[C@@H]1C=C(C)CC[C@@]13COC(=O)C)O2 AUGQEEXBDZWUJY-ZLJUKNTDSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- SAMRUMKYXPVKPA-VFKOLLTISA-N Enocitabine Chemical compound O=C1N=C(NC(=O)CCCCCCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 SAMRUMKYXPVKPA-VFKOLLTISA-N 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- OBMLHUPNRURLOK-XGRAFVIBSA-N Epitiostanol Chemical compound C1[C@@H]2S[C@@H]2C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 OBMLHUPNRURLOK-XGRAFVIBSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000056372 ErbB-3 Receptor Human genes 0.000 description 1
- 102000044591 ErbB-4 Receptor Human genes 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000605986 Fusobacterium nucleatum Species 0.000 description 1
- 230000037057 G1 phase arrest Effects 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241000192128 Gammaproteobacteria Species 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- JMBQKKAJIKAWKF-UHFFFAOYSA-N Glutethimide Chemical compound C=1C=CC=CC=1C1(CC)CCC(=O)NC1=O JMBQKKAJIKAWKF-UHFFFAOYSA-N 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010051922 Hereditary non-polyposis colorectal cancer syndrome Diseases 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 206010059017 Intestinal mass Diseases 0.000 description 1
- 238000001276 Kolmogorov–Smirnov test Methods 0.000 description 1
- 238000012313 Kruskal-Wallis test Methods 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 241001112693 Lachnospiraceae Species 0.000 description 1
- 229920001491 Lentinan Polymers 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 241000276420 Lophius piscatorius Species 0.000 description 1
- 206010050953 Lower gastrointestinal haemorrhage Diseases 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- IVDYZAAPOLNZKG-KWHRADDSSA-N Mepitiostane Chemical compound O([C@@H]1[C@]2(CC[C@@H]3[C@@]4(C)C[C@H]5S[C@H]5C[C@@H]4CC[C@H]3[C@@H]2CC1)C)C1(OC)CCCC1 IVDYZAAPOLNZKG-KWHRADDSSA-N 0.000 description 1
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 108010050619 Monokines Proteins 0.000 description 1
- 102000013967 Monokines Human genes 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- KGTDRFCXGRULNK-UHFFFAOYSA-N Nogalamycin Natural products COC1C(OC)(C)C(OC)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=C4C5(C)OC(C(C(C5O)N(C)C)O)OC4=C3C3=O)=C3C=C2C(C(=O)OC)C(C)(O)C1 KGTDRFCXGRULNK-UHFFFAOYSA-N 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000204306 Parabacteroides merdae Species 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000015731 Peptide Hormones Human genes 0.000 description 1
- 108010038988 Peptide Hormones Proteins 0.000 description 1
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 1
- 108010003044 Placental Lactogen Proteins 0.000 description 1
- 239000000381 Placental Lactogen Substances 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Porfiromycine Chemical compound O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000872831 Roseburia faecis Species 0.000 description 1
- 241000192031 Ruminococcus Species 0.000 description 1
- CGNLCCVKSWNSDG-UHFFFAOYSA-N SYBR Green I Chemical compound CN(C)CCCN(CCC)C1=CC(C=C2N(C3=CC=CC=C3S2)C)=C2C=CC=CC2=[N+]1C1=CC=CC=C1 CGNLCCVKSWNSDG-UHFFFAOYSA-N 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241001136694 Subdoligranulum Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- IWEQQRMGNVVKQW-OQKDUQJOSA-N Toremifene citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 IWEQQRMGNVVKQW-OQKDUQJOSA-N 0.000 description 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- UMILHIMHKXVDGH-UHFFFAOYSA-N Triethylene glycol diglycidyl ether Chemical compound C1OC1COCCOCCOCCOCC1CO1 UMILHIMHKXVDGH-UHFFFAOYSA-N 0.000 description 1
- FYAMXEPQQLNQDM-UHFFFAOYSA-N Tris(1-aziridinyl)phosphine oxide Chemical compound C1CN1P(N1CC1)(=O)N1CC1 FYAMXEPQQLNQDM-UHFFFAOYSA-N 0.000 description 1
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 1
- 241001147795 Tyzzerella nexilis Species 0.000 description 1
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- SPJCRMJCFSJKDE-ZWBUGVOYSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] 2-[4-[bis(2-chloroethyl)amino]phenyl]acetate Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 SPJCRMJCFSJKDE-ZWBUGVOYSA-N 0.000 description 1
- ZLWULWWXACZTPR-UHFFFAOYSA-N [ClH]=O Chemical compound [ClH]=O ZLWULWWXACZTPR-UHFFFAOYSA-N 0.000 description 1
- USDJGQLNFPZEON-UHFFFAOYSA-N [[4,6-bis(hydroxymethylamino)-1,3,5-triazin-2-yl]amino]methanol Chemical compound OCNC1=NC(NCO)=NC(NCO)=N1 USDJGQLNFPZEON-UHFFFAOYSA-N 0.000 description 1
- 108010023617 abarelix Proteins 0.000 description 1
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 1
- 229960002184 abarelix Drugs 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- QUHYUSAHBDACNG-UHFFFAOYSA-N acerogenin 3 Natural products C1=CC(O)=CC=C1CCCCC(=O)CCC1=CC=C(O)C=C1 QUHYUSAHBDACNG-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 101150092805 actc1 gene Proteins 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 108700025316 aldesleukin Proteins 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 229960003437 aminoglutethimide Drugs 0.000 description 1
- ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 1
- 229960002749 aminolevulinic acid Drugs 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- BBDAGFIXKZCXAH-CCXZUQQUSA-N ancitabine Chemical compound N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 BBDAGFIXKZCXAH-CCXZUQQUSA-N 0.000 description 1
- 229950000242 ancitabine Drugs 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 150000008209 arabinosides Chemical class 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 229940087620 aromasin Drugs 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- 230000007147 bacterial dysbiosis Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 108700002839 cactinomycin Proteins 0.000 description 1
- 229950009908 cactinomycin Drugs 0.000 description 1
- 229940088954 camptosar Drugs 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 229930188550 carminomycin Natural products 0.000 description 1
- XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 1
- XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 1
- 229960003261 carmofur Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229950001725 carubicin Drugs 0.000 description 1
- BBZDXMBRAFTCAA-AREMUKBSSA-N carzelesin Chemical compound C1=2NC=C(C)C=2C([C@H](CCl)CN2C(=O)C=3NC4=CC=C(C=C4C=3)NC(=O)C3=CC4=CC=C(C=C4O3)N(CC)CC)=C2C=C1OC(=O)NC1=CC=CC=C1 BBZDXMBRAFTCAA-AREMUKBSSA-N 0.000 description 1
- 229950007509 carzelesin Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- ZYVSOIYQKUDENJ-WKSBCEQHSA-N chromomycin A3 Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1OC(C)=O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](O[C@@H]3O[C@@H](C)[C@H](OC(C)=O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@@H]1C[C@@H](O)[C@@H](OC)[C@@H](C)O1 ZYVSOIYQKUDENJ-WKSBCEQHSA-N 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- 150000004814 combretastatins Chemical class 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 230000005574 cross-species transmission Effects 0.000 description 1
- 108010006226 cryptophycin Proteins 0.000 description 1
- 108010089438 cryptophycin 1 Proteins 0.000 description 1
- 108010090203 cryptophycin 8 Proteins 0.000 description 1
- 238000013211 curve analysis Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- URLVCROWVOSNPT-QTTMQESMSA-N desacetyluvaricin Natural products O=C1C(CCCCCCCCCCCC[C@@H](O)[C@H]2O[C@@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@H](C)O1 URLVCROWVOSNPT-QTTMQESMSA-N 0.000 description 1
- 210000001731 descending colon Anatomy 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- WVYXNIXAMZOZFK-UHFFFAOYSA-N diaziquone Chemical compound O=C1C(NC(=O)OCC)=C(N2CC2)C(=O)C(NC(=O)OCC)=C1N1CC1 WVYXNIXAMZOZFK-UHFFFAOYSA-N 0.000 description 1
- 229950002389 diaziquone Drugs 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000021004 dietary regimen Nutrition 0.000 description 1
- 235000020805 dietary restrictions Nutrition 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 210000004921 distal colon Anatomy 0.000 description 1
- 208000007784 diverticulitis Diseases 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
- 229950005454 doxifluridine Drugs 0.000 description 1
- NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 description 1
- 229950004683 drostanolone propionate Drugs 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229950000549 elliptinium acetate Drugs 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 229950011487 enocitabine Drugs 0.000 description 1
- 208000037902 enteropathy Diseases 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229950002973 epitiostanol Drugs 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- QSRLNKCNOLVZIR-KRWDZBQOSA-N ethyl (2s)-2-[[2-[4-[bis(2-chloroethyl)amino]phenyl]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound CCOC(=O)[C@H](CCSC)NC(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 QSRLNKCNOLVZIR-KRWDZBQOSA-N 0.000 description 1
- 229960005237 etoglucid Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940043168 fareston Drugs 0.000 description 1
- 229940087476 femara Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000013100 final test Methods 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229960004421 formestane Drugs 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229940044658 gallium nitrate Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 229940020967 gemzar Drugs 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 229960002972 glutethimide Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 231100000508 hormonal effect Toxicity 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960003685 imatinib mesylate Drugs 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 description 1
- 229950008097 improsulfan Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000012296 in situ hybridization assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000007413 intestinal health Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000003870 intestinal permeability Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 229940115286 lentinan Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000007477 logistic regression Methods 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- RVFGKBWWUQOIOU-NDEPHWFRSA-N lurtotecan Chemical compound O=C([C@]1(O)CC)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC=2OCCOC=2C=C1C=4CN1CCN(C)CC1 RVFGKBWWUQOIOU-NDEPHWFRSA-N 0.000 description 1
- 229950002654 lurtotecan Drugs 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- MQXVYODZCMMZEM-ZYUZMQFOSA-N mannomustine Chemical compound ClCCNC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CNCCCl MQXVYODZCMMZEM-ZYUZMQFOSA-N 0.000 description 1
- 229950008612 mannomustine Drugs 0.000 description 1
- 238000012067 mathematical method Methods 0.000 description 1
- 235000021274 meat intake Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229950009246 mepitiostane Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 238000013048 microbiological method Methods 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229940086322 navelbine Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000009099 neoadjuvant therapy Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229950009266 nogalamycin Drugs 0.000 description 1
- KGTDRFCXGRULNK-JYOBTZKQSA-N nogalamycin Chemical compound CO[C@@H]1[C@@](OC)(C)[C@@H](OC)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=C4[C@@]5(C)O[C@H]([C@H]([C@@H]([C@H]5O)N(C)C)O)OC4=C3C3=O)=C3C=C2[C@@H](C(=O)OC)[C@@](C)(O)C1 KGTDRFCXGRULNK-JYOBTZKQSA-N 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000004223 overdiagnosis Methods 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229960000952 pipobroman Drugs 0.000 description 1
- NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 description 1
- NUKCGLDCWQXYOQ-UHFFFAOYSA-N piposulfan Chemical compound CS(=O)(=O)OCCC(=O)N1CCN(C(=O)CCOS(C)(=O)=O)CC1 NUKCGLDCWQXYOQ-UHFFFAOYSA-N 0.000 description 1
- 229950001100 piposulfan Drugs 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 208000022131 polyp of large intestine Diseases 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 229940087463 proleukin Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- WOLQREOUPKZMEX-UHFFFAOYSA-N pteroyltriglutamic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(=O)NC(CCC(=O)NC(CCC(O)=O)C(O)=O)C(O)=O)C(O)=O)C=C1 WOLQREOUPKZMEX-UHFFFAOYSA-N 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 238000007637 random forest analysis Methods 0.000 description 1
- BMKDZUISNHGIBY-UHFFFAOYSA-N razoxane Chemical compound C1C(=O)NC(=O)CN1C(C)CN1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-UHFFFAOYSA-N 0.000 description 1
- 229960000460 razoxane Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011897 real-time detection Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 229950004892 rodorubicin Drugs 0.000 description 1
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 210000001599 sigmoid colon Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229950006315 spirogermanium Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229950001353 tretamine Drugs 0.000 description 1
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- PXSOHRWMIRDKMP-UHFFFAOYSA-N triaziquone Chemical compound O=C1C(N2CC2)=C(N2CC2)C(=O)C=C1N1CC1 PXSOHRWMIRDKMP-UHFFFAOYSA-N 0.000 description 1
- 229960004560 triaziquone Drugs 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- 208000022271 tubular adenoma Diseases 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 229940094060 tykerb Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 229960001055 uracil mustard Drugs 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
- C12Q1/06—Quantitative determination
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6851—Quantitative amplification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/686—Polymerase chain reaction [PCR]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
- C12Q1/689—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
- G01N33/721—Haemoglobin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Pathology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Toxicology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
a)任意に、上記被験体から単離された糞便試料においてFOBTを実施することと、
ここで、上記FOBTは、上記糞便試料中の潜血の存在の判断を含む;
b)上記被験体から単離された腸管試料(好ましくは糞便試料)において、以下の細菌マーカー:
ゲメラ・モルビロルム(Gemella Morbillorum)(GMLL)、
ペプトストレプトコッカス・ストマティス(Peptostreptococcus stomatis)(PTST)、及び、
バクテロイデス・フラジリス(Bacteroides fragilis)(BCTF)、
のうちの少なくとも1つ又はそれらの任意の組合せを定量化することと、
を含む、方法に関する。
a)任意に、上記被験体から単離された糞便試料においてFOBTを実施することと、
ここで、上記FOBTは、上記糞便試料中の潜血の存在の判断を含む、
b)上記被験体から単離された腸管試料(好ましくは糞便試料)において、以下の細菌マーカー:
ゲメラ・モルビロルム(GMLL)、
ペプトストレプトコッカス・ストマティス(PTST)、及び、
バクテロイデス・フラジリス(BCTF)、
のうちの少なくとも1つ又はそれらの任意の組合せを定量化することと、
を含む、方法に関する。
i.GMLLゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号1に特異的なオリゴヌクレオチド、
ii.PTSTゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号2に特異的なオリゴヌクレオチド、
iii.BCTFゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号3に特異的なオリゴヌクレオチド、
iv.BCTTゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号4に特異的なオリゴヌクレオチド、及び、
v.任意に、本明細書において上記に規定された真正細菌の定量化に適したオリゴヌクレオチド、
のうちの1つ以上を含む、キットを提供する。
「被験体」又は「個体」という用語は、哺乳動物として分類される全ての動物を指すため本明細書において同じ意味で使用され、飼育動物及び家畜、霊長類及びヒト、例えば、人間、非ヒト霊長類、ウシ、ウマ、ブタ、ヒツジ、ヤギ、イヌ、ネコ、又は齧歯類を含むがこれらに限定されない。被験体は、あらゆる年齢又は人種の男性又は女性の人間であることが好ましい。
第1の態様において、本発明は、被験体における結腸直腸進行新生物(AN)、進行腺腫(AA)、及び/又は結腸直腸癌(CRC)をスクリーニング、診断、及び/又はモニタリングする便潜血検査(FOBT)の特異度を高める又は偽陽性率を減らす方法であって、
a)任意に、上記被験体から単離された糞便試料においてFOBTを実施することと、
ここで、上記FOBTは、上記糞便試料中の潜血の存在の判断を含む;
b)上記被験体から単離された腸管試料(好ましくは糞便試料)において、以下の細菌マーカー:
ゲメラ・モルビロルム(GMLL)、
ペプトストレプトコッカス・ストマティス(PTST)、及び、
バクテロイデス・フラジリス(BCTF)、
のうちの少なくとも1つ又はそれらの任意の組合せを定量化することと、
を含む、方法に関する。
a)任意に、上記被験体から単離された糞便試料においてFOBTを実施することと、
ここで、上記FOBTは、上記糞便試料中の潜血の存在の判断を含む;
b)上記被験体から単離された腸管試料(好ましくは糞便試料)において、以下の細菌マーカー:
ゲメラ・モルビロルム(GMLL)、
ペプトストレプトコッカス・ストマティス(PTST)、及び、
バクテロイデス・フラジリス(BCTF)、
のうちの少なくとも1つ又はそれらの任意の組合せを定量化することと、
を含む、方法に関する。
61 gataatgtcg attttgaagc aatggcaatg cgcttaagtc ctattttaga ttctgttgtc
121 tatattttag atgtagaagg taatattctt gggtatgatt ctattgtaga ttattctaac
181 gaacgtatgg aagaaattat tcgtgcgagg aaagtgccta aagcttattt agatgcaaca
241 ttaaaagtat atgctacgaa ggttaatatt ccatttcaag atccgctttc tattttccca
301 gatgaagaga aagaaagatt tgatgggaat acctatactg taattttacc aataagaggc
361 gggggagaac gccttggaac tcttgttata ggaagaatgg ataatgactt tcaagatgat
421 gatttggtgt tagcagaata tgcgtcaaca gtagtaggaa ttgaaattct tcacgaaaaa
481 caagataaag aaaaaaatct agctagagac aaagatatgg tgaatatggc tcttaattcg
541 ttatcatatt cagaaaaaga agcaattgaa catattttca gagaattaga tgggacagaa
601 ggactactta tcgcaagtaa aattgcagat agagtaggaa ttactcgctc agttattgtt
661 aatgcactta gaaaattaga aagtgcaggt attatagagt caaaatcatt aggtatgaaa
721 ggtacttata taaaagtact taaagaatat tttttagaat taatgttttc taatgaattt
781 taa
61 attaaagatt tctctgacat gtccggaatt agtactgctc tgcttagtca attagaaaga
121 ggtgttggaa accctagcct gagtgtattg aactctatag cagataccat gaatactagc
181 ctctcctctt tattagaaga acctgttgtt ttagaaaacc tggttagaag gtctgacacc
241 ctatccacta ttgtctaccc atgtaggaac aaccttgaat ttcagttgct cacaactagg
301 tctactactc agagcatcaa ccttgtaaga ataatatttc atgctcattc agaaactaat
361 taccagccac ttggaaaaac cgtttctgat gatataatcc acattgaaaa gggcagtatt
421 attgttcaaa ctgatgatgg taagtctatt caactaaaaa aaggtgatac tatgaggata
481 ccacctgacc ttaggtataa attcaagaat atttctgtac acaaggcaca tatgatttgt
541 gccactaata aacttgaagt aagataa
61 aaactggaag tgcgaataga gaatgaaacc gtttggttga cacaagcaca aattgttaac
121 ttattccagt caagtaaagc caatatcagt gagcatataa gaaatatata tgactcagat
181 gaattatctg ctgaatcaac tgttcggaaa ttccgaacag ttcgaatgga aggtaataga
241 aaggttaccc gcattcttga atattataat ctggatatga ttatttccgt aggttatcgt
301 gtgaattcca agcgaggagt ccagttccgc caatggtcaa caggagtact taaagaatat
361 ctattaaaag gctacgcaat caatcagcgc gtggagcagt tggaaaacaa agcaaacacc
421 catgaccggc aactggaaga gttaacaaac aaagtcgact ttttcgtccg gacttcatta
481 cctcctattg aaggtgtctt tttcaacgga cagattttcg atgcctatgt cttttccgct
541 cagttgataa agtctgcaaa gtcatcttta gtattgattg acaactttgt cgatgaaagc
601 gtgctcttac tattgagtaa acgtttgccc ggagtgactt ctatcatata taccaagcaa
661 gtaactccac agttagaatt agatttgaca aagcacaaca gtcaataccc ccaatag
40歳以上で原因不明の体重減少及び腹痛を伴う場合に、又は、
50歳以上で原因不明の直腸出血を伴う場合に、又は、
60歳以上で:
鉄欠乏性貧血、若しくは、
排便習慣の変化、
を伴う場合に、又は、
検査で糞便中に潜血が見られる場合に、
成人を紹介する。
腹痛、
排便習慣の変化、
体重減少、
鉄欠乏性貧血、
のいずれかを伴う50歳未満の成人においては、結腸直腸癌についての癌経路が疑われた紹介(例えば、2週間以内の面会予約の場合)を考慮する。
50歳以上で原因不明の、
腹痛、若しくは、
体重減少、
を伴う成人、又は、
60歳未満で:
排便習慣の変化、若しくは、
鉄欠乏性貧血、
を伴う成人、又は、
60歳以上で、かつ鉄欠乏状態でなくても貧血を有する成人、
においては、結腸直腸癌を評価する糞便中潜血についての検査を提供する。
高まったリスクの被験体
以前の結腸内視鏡検査でポリープの病歴を有する被験体、
結腸直腸癌を有する被験体、及び、
結腸直腸癌又は腺腫性ポリープの家族歴を有する被験体、
であって、
i.60歳より若い第一度近親者若しくは任意の年齢の2人以上の第一度近親者においてCRC若しくは腺腫性ポリープのいずれかを含む、被験体、及び/又は、
ii.60歳以上の第一度近親者若しくはCRCを有する2人の第二度近親者においてCRC若しくは腺腫性ポリープのいずれかを含む、被験体、
高いリスク
遺伝子検査によって家族性大腸腺腫症(FAP)と診断された被験体、又は遺伝子検査なしでFAPが疑われる被験体、
遺伝性非ポリポーシス大腸癌(HNPCC又はリンチ症候群)を有する被験体、又は遺伝子検査なしで家族歴に基づいてHNPCCの高まったリスクの被験体、及び、
慢性潰瘍性大腸炎又はクローン病等の炎症性腸疾患を有する被験体、
が挙げられ得る。
61 cgttatcatg cccgtccggt aagttttgag accgtcaata ccgagaaact ggcttatcgc
121 atccatgatc gctccacatt aagagtatcg gacattattt caaccttgga agaactgaaa
181 aatgaagtag ctcagtgcct cctggaaggt aaaaaggtgc atgtcgatgg attaggattc
241 tttcaggtca ctctttcctg cgaagaagaa atacgtaacc cgaaagacaa acgtgtgcac
301 cgggtaaaat tgaaagctat aaagtttaaa gctgataaag aattgaaagg ggaattgtgt
361 cacatgaaat tccagcgttc taaaatcaga ccgcactccg ccaatttatc agaagtagaa
421 atagacatga aactaactga atattttgct gaaaatcaga ttatcacccg gaaagatttt
481 caatatctct gcggaatgac acaaatcact gcatatcgcc atatcaagag gttaatggca
541 gaaaagaaat tgcaaaataa agggacgatc tatcaaccga tatatactcc ggttccgggt
601 aattacaggg tatcggtgga tttaaaatat aaagaacaat ga
EUB2フォワード(配列番号5):ACTCCTACGGGAGGCAGCAGT
EUB2リバース(配列番号6):GTATTACCGCGGCTGCTGGCAC
のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列も使用され得る。
c)b)で決定された細菌マーカーのレベルから組合せスコア(combined score)を計算することと、
d)FOBT陽性被験体を、c)で得られた組合せスコアに従って、AN、AA、及び/又はCRCを有する又はそれらの高まったリスクを表すとして分類することと、
を更に含む。
e)糞便試料中のGMLL、PTST、BCTF、及び/又はBCTTのいずれかの量と、対応する参照値とを比較すること、
を更に含み得て、ここで、
f)対応する参照値に対するFOBT陽性被験体の試料におけるGMLL、PTST、及び/又はBCTFの量の増加、並びにBCTTの量の減少が、AN、AA、及び/又はCRCの指標である。
61 cggctaacta cgtgccagca gccgcggtaa aacgtaggtc acaagcgttg tccggaatta
121 ctgggtgtaa agggagcgca ggcgggaaga caagttggaa gtgaaatcca tgggctcaac
181 ccatgaactg ctttcaaaac tgtttttctt gagtagtgca caggtaggcg gaattcccgg
241 tgtagcggtg gaatgcgtag atatcgggag gaacaccagt ggcgaaggcg gcctactggg
301 caccaactga cgctgaggct cgaaagtgtg ggtagcaaac aggattagat accctggtag
361 tccacactgt aaacgatgat tactaggtgt tggaggattg accccttcag tgccgcagtt
421 aacacaataa gtaatccacc tggggagtac gaccgcaagg ttgaaactca aaggaattga
481 cggac
61 gacggaagcc gcggttccac gtaagtcaca agcgttgtcc ggaattactg ggtgtaaagg
121 gagcgcaggc gggaagacaa gttggaagtg aaatccatgg gctcaaccca taaactgctt
181 tcctaactgt ttttcttgag tagtgcacag gtaggcggaa ttcccggtgt agcggtggaa
241 tgcctagata tcgggaggaa caccattggc gaaggcggcc tactggactg caactgacgc
301 tgaggctcga aagtgtgggt agcaaacagg attagatacc ctggtagtcc actccgtaaa
361 ccatgattac tacgtgttgg aggattgacc ccttctgtgc cgcagataac acaataagta
421 atccacctgg ggagtacgac cgcccggttg agactcacag gaattgacgg actc
61 cgccgcgtga gcgatgaagt atttcggtat gtaaagctct atcagcaggg aagaaaatga
121 cggtacctga ctaagaagcc ccggctaaat acgtgccagc agccgcggta atacgtatgg
181 tgcaagcgtt atccggattt actgggtgta aagggagcgt agacggagtg gcaagtctga
241 tgtgaaaacc cggggctcaa ccccgggact gcattggaaa ctgtgcatct agagtgtcgg
301 agaggtaagc ggaattccta gtgtagcggt gaaatgcgta gatattagga ggaacaccag
361 tggcgaaggc ggcttactgg acgataactg acgctgaggc tcgaaagcgt ggggagcaaa
421 caggattaga taccctggta gtccacgccg taaacgatga ctactaggtg tcggggagca
481 cagctcttcg gtgccgcagc aaacgcaata agtattccac ctggggagta cgttcgcaag
541 aatgaaactc acagaatttg acggag
61 tgtcagatcg ctgaacttgc ggcgttagtt gcttttgacg gaaagcgtca gcagctgatc
121 ggggatgcgg gagatgtgct ggattcggaa aatccgcttc tgcaggaaaa atatggactg
181 ttactggcac agctgttcca tgttaatata gaagagatag atacattgcc accggaacgc
241 attcttgaga caatcaagat gtggaatcag tctttaaggt gtgcagatat cacagagacg
301 gtaaatggta ttttactgca gcagacatgt tgcaggcggg catatatccg gggagcattt
361 ttagcaggtg gatcgatcag tgatccgaat aagtcttatc attttgagat tgtctgccgg
421 gaaattgcgc aggcgaaaca gcttcaggat gcaatcaaca gttttgagat ggaagcaaag
481 atcgtagaac gaaagaaaca ccaggtcgta tatttaaagg aaggtgccca gatcgtggat
541 atgttaaata tcatggaagc acatgtggca ctgatgaatc ttgaaaatgt gcgtatctta
601 aaagaaatga gaaattctgt caaccgaaag gtaaattgtg agacggcaaa tatcagcaag
661 actgtggcgg cagccgtaaa acagcttggc gatattgaat atattaaaca gaatgcaggc
721 ttagacagtc tgcctgaaaa cctaaaagaa atggcgttgc tgcggttaga gtatccggat
781 acaccgctta aggaactggg aacatatctc gatcctccgg tcggaaaatc gggagtgaac
841 cacaggctgc gcaggatcag tgagattgca gatgagctgc gtgaaaaaga ataa
61 cgttccgccc tgttctccaa gctgagccgt aacatcaccg tcgcggcccg tcttggcaac
121 gaccccaacc cggacaacaa cgcctccctc gccgctgccg tggccaaggc caaggctcag
181 tccatgccca aggacaagat caaggccgcc atcgacaagg ccttcggttc cggcgccgac
241 gccgccgtgt acgagaacat cgtgtacgag ggctacggcc cggccggtgt tgccgtgtac
301 gtcgagtgcc tgaccgacaa ccgcaaccgc accgccgccg atgtccgctc cgccttctcc
361 cacgctggcg gcaacctggg caccaccggc tccgttgcct tccagttcga gcgcaagggc
421 caggtcgtgg tctccaagca gatcgtcgac ccgaacgaca agaaggagaa cctcatggcc
481 aacggcgctg ccggcgatga ggaagagttc atgatggtca tcgccgaggc cggtggcgac
541 gactacgagg acgccggtga cgagtgggtc gtgtggaccg ccgcgggcga cctcatggcc
601 gtgtccaagg gcatcgaggc tcagggcatc gaggtcaagg gtgccgagct caccatggtc
661 ccgaccaccc cgacggccgt ctccggcgcc gacgccaaga aggtccagcg cctcatcgac
721 cgcctcgagg acctggacga cgtccaggac gtgtactcca ccatggacat gaccgacgag
781 gtcatcgctg ccctcgaaga ggagtaa
61 gagagagagc ttgctttctc gagcgagtgg cgaacgggtg agtaacgcgt gaggaacctg
121 cctcaaagag ggggacaaca gttggaaacg actgctaata ccgcataagc ccacagctcg
181 gcatcgagca gagggaaaag gagcaatccg ctttgagatg gcctcgcgtc cgattagcta
241 gttggtgagg taatggccca ccaaggcaac gatcggtagc cggactgaga ggttgaacgg
301 ccacattggg actgagacac ggcccagact cctacgggag gcagcagtgg ggaatattgc
361 acaatggggg aaaccctgat gcagcgacgc cgcgtggagg aagaaggtct tcggattgta
421 aactcctgtt gttgaggaag ataatgacgg tactcaacaa ggaagtgacg gctaactacg
481 tgccagcagc cgcggtaaaa cgtaggtcac aagcgttgtc cggaattact gggtgtaaag
541 ggagcgcagg cgggaagaca agttggaagt gaaatctatg ggctcaaccc ataaactgct
601 ttcaaaactg tttttcttga gtagtgcaga ggtaggcgga attcccggtg tagcggtgga
661 atgcgtagat atcgggagga acaccagtgg cgaaggcggc ctactgggca ccaactgacg
721 ctgaggctcg aaagtgtggg tagcaaacag gattagatac cctggtagtc cacaccgtaa
781 acgatgatta ctaggtgttg gaggattgac cccttcagtg ccgcagttaa cacaataagt
841 aatccacctg gggagtacga ccgcaaggtt gaaactcaaa ggaattgacg ggggcccgca
901 caagcagtgg agtatgtggt ttaattcgac gcaacgcgaa gaaccttacc aagtcttgac
961 atcctgcgac gatgctggaa acagtatttt ccttcgggac gcagagacag gtggtgcatg
1021 gttgtcgtca gctcgtgtcg tgagatgttg ggttaagtcc cgcaacgagc gcaaccctta
1081 ctgtcagtta ctacgcaaga ggactctggc aggactgccg ttgacaaaac ggaggaaggt
1141 ggggatgacg tcaaatcatc atgcccttta tgacttgggc tacacacgta ctacaatggc
1201 gttaaacaaa gagaagcaag accgcgaggt ggagcaaaac tcagaaacaa cgtcccagtt
1261 cggactgcag gctgcaactc gcctgcacga agtcggaatt gctagtaatc gtggatcagc
1321 atgccacggt gaatacgttc ccgggccttg tacacaccgc ccgtcacacc atgagagccg
1381 gggggacccg aagtcggtag tctaaccgca aggaggacgc cgccgaaggt aaaactggtg
1441 attggggtga agtcgtaaca aggtac
61 cggtgtgtac aaggcccggg aacgtattca ccgtggcatt ctgatccacg attactagcg
121 attccgactt catggagtcg agttgcagac tccaatccgg actacgacgc actttatgag
181 gtccgcttgc tctcgcgagg tcgcttctct ttgtatgcgc cattgtagca cgtgtgtagc
241 cctggtcgta agggccatga tgacttgacg tcatccccac cttcctccag tttatcactg
301 gcagtctcct ttgagttccc ggccggaccg ctggcaacaa aggataaggg ttgcgctcgt
361 tgcgggactt aacccaacat ttcacaacac gagctgacga cagccatgca gcacctgtct
421 cacggttccc gaaggcacat tctcatctct gaaaacttcc gtggatgtca agaccaggta
481 aggttcttcg cgttgcatcg aattaaacca catgctccac cgcttgtgcg ggcccccgtc
541 aattcatttg agttttaacc ttgcggccgt actccccagg cggtcgactt aacgcgttag
601 ctccggaagc cacgcctcaa gggcacaacc tccaagtcga catcgtttac ggcgtggact
661 accagggtat ctaatcctgt ttgctcccca cgctttcgca cctgagcgtc agtcttcgtc
721 cagggggccg ccttcgccac cggtattcct ccagatctct acgcatttca ccgctacacc
781 tggaattcta cccccctcta cgagactcaa gcttgccagt atcagatgca gttcccaggt
841 tgagcccggg gatttcacat ctgacttaac aaaccgcctg cgtgcgcttt acgcccagta
901 attccgatta acgcttgcac cctccgtatt accgcggctg ctggcacgga gttagccggt
961 gcttcttctg cgggtaacgt caatgagcaa aggtattaac tttactccct tcctccccgc
1021 tgaaagtact ttacaacccg aaggccttct tcatacacgc ggcatggctg catcaggctt
1081 gcgcccattg tgcaatattc cccactgctg cctcccgtag gagtctggac cgtgtctcag
1141 ttccagtgtg gctggtcatc ctctcagacc agctagggat cgtcgcctag gtgagccgtt
1201 accccaccta ctagctaatc ccatctgggc acatccgatg gcaagaggcc cgaaggtccc
1261 cctctttggt cttgcgacgt tatgcggtat tagctaccgt ttccagtagt tatccccctc
1321 catcaggcag tttcccagac attactcacc cgtccgccac tcgtcagcaa agaagcaagc
1381 ttcttcctgt taccgttcga cttgcatgtg ttaggcctgc cgccagcgtt caatctgagc
1441 catgatcaaa ct
更なる態様において、本発明は、AN、AA、及び/又はCRCを有する被験体を治療する方法であって、上記被験体が、本明細書で上記に記載されるようにスクリーニング、診断、及び/又はモニタリングする方法によって選択されており、かつ上記方法が、被験体に抗癌療法薬を投与することを更に含む、方法を提供する。
別の態様において、本発明は、GMLL、PTST、BCTF、又はBCTTのいずれかを定量化するのに適したキットであって、以下の試薬:
i.GMLLゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号1に特異的なオリゴヌクレオチド、
ii.PTSTゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号2に特異的なオリゴヌクレオチド、
iii.BCTFゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号3に特異的なオリゴヌクレオチド、
iv.BCTTゲノムに特異的なオリゴヌクレオチド、好ましくは配列番号4に特異的なオリゴヌクレオチド、及び、
v.任意に、本明細書で上記に規定された真正細菌の定量化に適したオリゴヌクレオチド、
のうちの1つ以上を含む、キットを提供する。
配列番号1に特異的なオリゴヌクレオチドは、配列番号22若しくは配列番号23のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、及び/又は、
配列番号2に特異的なオリゴヌクレオチドは、配列番号24若しくは配列番号25のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、及び/又は、
配列番号3に特異的なオリゴヌクレオチドは、配列番号26若しくは配列番号27のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、及び/又は、
配列番号4に特異的なオリゴヌクレオチドは、配列番号30若しくは配列番号31のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、及び/又は、
真正細菌の定量化に適したオリゴヌクレオチドは、配列番号5、配列番号6、配列番号14、若しくは配列番号15のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである。
配列番号24若しくは配列番号25のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド、
配列番号26若しくは配列番号27のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド、及び、
配列番号30若しくは配列番号31のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド、及び、
任意に、真正細菌の定量化に適したオリゴヌクレオチド(好ましくは、配列番号5、配列番号6、配列番号14、若しくは配列番号15のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド)、
を含み、
任意に、被験体から単離された糞便試料中の上記細菌マーカーのレベルを決定する際の上記試薬の使用についての使用説明書を更に含む、キットに関する。
配列番号24を含む若しくはそれのみからなるプライマー、配列番号25を含む若しくはそれのみからなるプライマー、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む若しくはそれのみからなるプライマー、
配列番号26を含む若しくはそれのみからなるプライマー、配列番号27を含む若しくはそれのみからなるプライマー、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む若しくはそれのみからなるプライマー、及び、
配列番号30を含む若しくはそれのみからなるプライマー、配列番号31を含む若しくはそれのみからなるプライマー、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む若しくはそれのみからなるプライマー、並びに、
任意に、真正細菌の定量化に適したオリゴヌクレオチド(好ましくは、配列番号5を含む若しくはそれのみからなるプライマー、配列番号6を含む若しくはそれのみからなるプライマー、配列番号14を含む若しくはそれのみからなるプライマー、又は配列番号15を含む若しくはそれのみからなるプライマー、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む若しくはそれのみからなるプライマー)、
を含み、
任意に、被験体から単離された糞便試料中の上記細菌マーカーのレベルを決定する際の上記試薬の使用についての使用説明書を更に含む、キットに関する。
1.被験体における結腸直腸進行新生物(AN)、進行腺腫(AA)、及び/又は結腸直腸癌(CRC)をスクリーニング、診断、及び/又はモニタリングする便潜血検査(FOBT)の特異度を高める又は偽陽性率を減らす方法であって、上記FOBTは、被験体から単離された糞便試料中の潜血の存在の判断を含み、上記方法は、上記被験体から単離された糞便試料において、少なくとも以下の細菌マーカー:
ペプトストレプトコッカス・ストマティス(PTST)、
バクテロイデス・フラジリス(BCTF)、及び、
バクテロイデス・テタイオタオミクロン(BCTT)、
を定量化することとを更に含み、ここで、結腸直腸進行新生物(AN)という用語は、CRC及び進行腺腫(AA)を包含する、方法。
a)上記被験体から単離された糞便試料においてFOBTを実施することと、
ここで、FOBTは、上記糞便試料中の潜血の存在の判断を含む;
b)上記被験体から単離された糞便試料においてペプトストレプトコッカス・ストマティス(PTST)、バクテロイデス・フラジリス(BCTF)、及びバクテロイデス・テタイオタオミクロン(BCTT)からなる細菌マーカーを少なくとも定量化することと、
c)b)で決定された細菌マーカーのレベルから組合せスコアを計算することと、
d)FOBT陽性被験体を、c)で得られた組合せスコアに従って、AN、AA、及び/又はCRCを有することの高まったリスクを表すとして分類することと、
を含む、方法。
e)糞便試料中のPTST、BCTF、及びBCTTの量と、対応する参照値とを比較すること、
を更に含み、ここで、
f)対応する参照値に対するFOBT陽性被験体の試料におけるPTST及びBCTFの量の増加、並びにBCTTの量の減少が、AN、AA、及び/又はCRCの指標である、ヒト被験体におけるAN、AA、及び/又はCRCをスクリーニング、診断、及び/又はモニタリングする方法。
配列番号2に特異的なオリゴヌクレオチド、
配列番号3に特異的なオリゴヌクレオチド、及び、
配列番号4に特異的なオリゴヌクレオチド、
任意に、真正細菌の定量化に適したオリゴヌクレオチド、
を含み、
任意に、被験体から単離された糞便試料中の上記細菌マーカーのレベルを決定する際の上記試薬の使用についての使用説明書を更に含む、キット。
配列番号2に特異的なオリゴヌクレオチドは、配列番号24若しくは配列番号25のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、及び/又は、
配列番号3に特異的なオリゴヌクレオチドは、配列番号26若しくは配列番号27のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、及び/又は、
配列番号4に特異的なオリゴヌクレオチドは、配列番号30若しくは配列番号31のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、及び/又は、
真正細菌の定量化に適したオリゴヌクレオチドは、配列番号5、配列番号6、配列番号14、若しくは配列番号15のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチドである、節22に記載のキット。
研究集団
プライマリーヘルスケア及びセカンダリーヘルスケアからオウレンセ総合病院(Complexo Hospitalario de Ourense)(スペイン、オウレンセ)へと診断的結腸内視鏡検査のために紹介されたCRCに関連する症状を有する333人の継続患者からなるコホートを採用した(表1)。除外基準は、(1)CRCスクリーニングのために結腸内視鏡検査を受けている無症状の被験体、(2)サーベイランス結腸内視鏡検査を受けている結腸疾患の既往歴を有する患者、(3)入院を必要とする患者、(4)症状が評価前3ヶ月以内に止まった患者、及び(5)組み入れる前の前月以内に抗生物質治療を受けた患者であった。研究プロトコルは、ビーゴ大学総合病院のバイオバンク(Biobanco del Complexo Hospitalario Universitario de Vigo)(スペイン、ビーゴ)によって承認された。全ての研究患者から、書面によるインフォームドコンセントを得た。
結腸内視鏡検査の前及び腸洗浄の前に、滅菌糞便容器内に1回の排便から便試料を収集するよう参加者に求めた。容器に入れた後すぐに試料を凍結した。次に、被験体は試料を病院に持ち込み、そこでは短期間の貯蔵のために-20℃で凍結させておき、ジローナ(スペイン)にあるGoodGut S.L.の施設に到着した後-80℃で貯蔵した。便試料の収集を誤っていたため、合計11人の被験体を研究から除外した。
NucleoSpin Soilキット(Macherey-Nagel GMbH & Co.、ドイツ、デューレン)を使用して、均質化後に凍結糞便試料からゲノムDNAを抽出した。製造業者の使用説明書に従い、最終的にDNAを最終容量100μlのSE溶出バッファー中で溶出させ、使用するまで-20℃で貯蔵した。Qubit蛍光定量(ThermoFisher Scientific、米国、ウォルサム)を用いて、DNA濃度を決定した。全ての試料を8ng/μlの最終濃度に調整し、再度定量化した。
標的とされる特定の細菌配列は、真正細菌(EUB)、B10(ベストマッチBLAST フィーカリバクテリウム・プラウスニッツィイ)、B46(ベストマッチBLAST サブドリグラニュラム・バリアビレ)、B48(ベストマッチBLAST ルミノコッカス属の一種、ロゼブリア属の一種、コプロコッカス属の一種)、ロゼブリア・インテスティナリス(RSBI)、ゲメラ・モルビロルム(GMLL)、ペプトストレプトコッカス・ストマティス(PTST)、バクテロイデス・フラジリス(BCTF)、コリンセラ・インテスティナリス(CINT)、及びバクテロイデス・テタイオタオミクロン(BCTT)の10種であった。
CRC特異的なバイオマーカー分析で使用されたものと同じ試料を使用して、オウレンセ総合病院でFIT分析を実施した。Cubiella, J. et al., 2016で以前に記載されたように、OCセンサーの収集チューブを使用して糞便ヘモグロビン決定用の便試料を分析し、CRC、ポリープ、及び憩室炎等の障害に関連する消化管出血を検出する自動式OCセンサー(栄研化学株式会社、日本、東京)を使用してアッセイを行った。OCセンサーの試料チューブ内のサンプルバッファーは、収集から分析まで、試料の最適な安定性及び安全な輸送を保証する。陽性の検査は、100ng/mL(糞便1g当たり20μgのHb;FIT100)以上の糞便ヘモグロビン濃度を有する検査であった。
定性分析の観点から、得られたCt値がそのダイナミックレンジ内に含まれていない場合に、バイオマーカーが存在しないとみなした。全ての統計分析を、SPSS 23.0統計パッケージ(IBM、米国、ニューヨーク市)を使用して実施した。有意水準は、P値≦0.05の場合に確立された。
各診断(正常な結腸内視鏡検査、非進行腺腫、進行腺腫、CRC)につき、各細菌マーカーの相対的存在量を決定した(図1)。結腸内視鏡検査の診断にかかわらず、3種の異なる酪酸産生種(B10、B46、及びB48)が最も優勢なバイオマーカーであり、それぞれ20.4%、19.0%、及び20.0%の相対的存在量値を有した。GMLL及びPTSTは、CRC集団において、正常な結腸内視鏡検査の個体(それぞれ、p=0.006及びp<0.001)又は非進行腺腫の被験体(それぞれ、p=0.047及びp<0.001)よりも有意に豊富であった。有意差を有しないが、B46が進行腺腫を有する被験体よりもCRC患者において豊富である傾向が観察され得た(p=0.087)。興味深いことに、EUBの存在量は、新生物の状態にかかわらず一定に維持されていた。異なるCRC病期(0、I、II、III、及びIV)間の比較により、どの細菌マーカーの存在量にも有意差は示されなかった。
被験体を以下のようにグループ分けした後に、細菌マーカーの相対的存在量を比較した:(1)正常な結腸内視鏡検査、(2)新生物(非進行腺腫+進行腺腫+CRC)、(3)進行新生物(進行腺腫+CRC)、及び(4)CRC(図2)。PTSTは、新生物病変と相関性が高いことが判明した(p<0.001)。進行新生物病変の検出に関して、GMLL、PTST、及びBCTFは、それらを検出する潜在的なバイオマーカーであった(それぞれ、p=0.006、p<0.001、及びp=0.030)。保有率に関して、これらの3種の日和見病原体は、健康な被験体(GMLL、53.5%;PTST、26.1%;及びBCTF、29.8%)よりも進行新生物を有する患者(GMLL、64.9%;PTST、58.4%;及びBCTF、44.7%)においてより多く見られた。
一方で、FIT100(糞便1g当たり20μgのHb)を使用した場合に、正常な結腸内視鏡検査を伴う又は非進行腺腫を有する被験体と進行新生物を有する被験体との間に有意差が観察された(p<0.001)。正常な結腸内視鏡検査を示した被験体の17.1%(19人)及び非進行腺腫を有した被験体の24.3%(27人)がFIT陽性値を示した。これらの結果は、進行新生物の検出について、それぞれ84.0%及び81.0%の感度及び特異度、並びにそれぞれ58.0%及び94.0%の陽性予測値及び陰性予測値(AUC=0.828、95.0%CI(0.773~0.883))を得ることにつながった。他方で、FIT50(糞便1g当たり10μgのHb)を使用した場合に、正常な結腸内視鏡検査を示した被験体の21.1%(27人)及び非進行腺腫を有した被験体の24.2%(31人)が偽陽性の結果を示した。FIT50は、進行新生物の検出について、それぞれ91.0%及び76.0%の感度及び特異度、並びにそれぞれ55.0%及び96.0%の陽性予測値及び陰性予測値(AUC=0.836、95.0%CI(0.787~0.886))を得ることにつながった。細菌マーカー単独の場合の感度値ははるかに低く、GMLLについて39.0%(AUC=0.622、95.0%CI(0.541~0.694))であり、PTSTについて53.0%(AUC=0.710、95.0%CI(0.628~0.776))であり、かつBCTFについて33.0%(AUC=0.571、95.0%CI(0.499~0.656))であったのに対して、特異度値は同等であった。
1. International Agengy for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. (Accessed: 7th November 2017)
2. Wilson, M. Microbial Inhabitants of Humans: Their Ecology and Role in Health and Disease. (Cambridge, 2005).
3. Brenner, H., Kloor, M. & Pox, C. P. Colorectal cancer. Lancet 383, 1490-1502 (2014).
4. Zauber, A. G. The Impact of Screening on Colorectal Cancer Mortality and Incidence - Has It Really Made a Difference? Dig. Dis. Sci. 60, 681-691 (2015).
5. Elmunzer, B. J. et al. Effect of Flexible Sigmoidoscopy-Based Screening on Incidence and Mortality of Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLOS Med. 9, (2012).
6. Rex, D. K. et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am. J. Gastroenterol. (2017). doi:10.1038/ajg.2017.174
7. Quintero, E. et al. Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening. N Engl J Med 366, 697-706 (2012).
8. Young, P. E. & Womeldorph, C. M. Colonoscopy for Colorectal Cancer Screening. J. Cancer 4, 217-226 (2013).
9. Rutter, C. M. et al. Adverse Events after Screening and Follow-up Colonoscopy. Cancer Causes Control 23, 289-296 (2012).
10. Sieg, A., Hachmoeller-Eisenbach, U. & Eisenbach, T. Prospective evaluation of complications in outpatient GI endoscopy: A survey among German gastroenterologists. Gastrointest. Endosc. 53, 620-627 (2001).
11. Gatto, N. M. et al. Risk of perforation after colonoscopy and sigmoidoscopy: a population-based study. J. Natl. Cancer Inst. 95, 230-6 (2003).
12. Sanford, K. W. & McPherson, R. A. Fecal Occult Blood Testing. Clin. Lab. Med. 29, 523-541 (2009).
13. Stracci, F., Zorzi, M., Grazzini, G. & Efird, J. T. Colorectal cancer screening: tests, strategies, and perspectives. (2014). doi:10.3389/fpubh.2014.00210
14. Brenner, H. & Tao, S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur. J. Cancer 49, 3049-3054 (2013).
15. Shapiro, J. A. et al. A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for Colorectal Cancer Screening. Nat. Publ. Gr. (2017). doi:10.1038/ajg.2017.285
16. Mousavinezhad, M., Majdzadeh, R., Akbari Sari, A., Delavari, A. & Mohtasham, F. The effectiveness of FOBT vs. FIT: A meta-analysis on colorectal cancer screening test. Med. J. Islam. Repub. Iran 30 (2016).
17. Goede, S. L. et al. Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening. doi:10.1371/journal.pone.0172864 (2017).
18. Borges-Canha, M., Portela-Cidade, J. P., Dinis-Ribeiro, M., Leite-Moreira, A. F. & Pimentel-Nunes, P. Role of colonic microbiota in colorectal carcinogenesis: A systematic review. Rev esp enfeRm dig 107, 659-671 (2015).
19. Mira-Pascual, L. et al. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J. Gastroenterol. 50, 167-179 (2014).
20. Sobhani, I. et al. Microbial Dysbiosis in Colorectal Cancer (CRC) Patients. PLoS One 6, (2011).
21. Jun, X. et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes 138-147 (2010). doi:10.1080/19490976.2016.1241933
22. Kostic, A. D. et al. Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment. Cell Host Microbe 14, 207-215 (2013).
23. Zackular, J. P., Rogers, M. A. M., Ruffin, M. T. & Schloss, P. D. The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev. Res. (Phila). 7, 1112-21 (2014).
24. Joshi, A. D. et al. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry (2015).
25. Dulal, S. & Keku, T. O. Gut Microbiome and Colorectal Adenomas. Cancer J. 20, 225-231 (2014).
26. Zeller, G. et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol. Syst. Biol. 10, 766-766 (2014).
27. Marchesi, J. R. et al. Towards the Human Colorectal Cancer Microbiome. PLoS One 6, e20447 (2011).
28. Mas de Xaxars Rivero, T. Descripcio i quantificacio de la microbiota intestinal associada al cancer colorectal. (2012).
29. Serra-Pages, M., Garcia-Gil, J., Mas de Xarxars, T. & Aldeguer, X. PCT/EP2015/054451. Biomarkers for early detection, risk screening and monitoring of colorectal cancer and adenomatous polyps. (2015).
30. Cubiella, J. et al. Development and external validation of a faecal immunochemical test-based prediction model for colorectal cancer detection in symptomatic patients. BMC Med. 14, 128 (2016).
31. Levin, B. et al. Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA. Cancer J. Clin. 58, 130-160 (2008).
32. Brenner, H., Altenhofen, L., Stock, C. & Hoffmeister, M. Prevention, Early Detection, and Overdiagnosis of Colorectal Cancer Within 10 Years of Screening Colonoscopy in Germany. Clin. Gastroenterol. Hepatol. 13, 717-723 (2015).
33. Shah, R. et al. Biomarkers for Early Detection of Colorectal Cancer and Polyps: Systematic Review. Cancer Epidemiol. Biomarkers Prev. 23, 1712-1728 (2014).
34. Wang, T. et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 6, 320-329 (2011).
35. Garrett, W. S. Cancer and the microbiota. Science (80-. ). 348, 80-86 (2015).
36. Kelly, D. & Mulder, I. E. Microbiome and immunological interactions. Nutr. Rev. (2012). doi:10.1111/j.1753-4887.2012.00498.x
37. Feng, Q. et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat. Commun. 6, (2015).
38. Gao, Z. et al. Microbiota disbiosis is associated with colorectal cancer. (2015). doi:10.3389/fmicb.2015.00020
39. Zhao, L., Zhang, X., Zuo, T. & Yu, J. The Composition of Colonic Commensal Bacteria According to Anatomical Localization in Colorectal Cancer. Engineering 3, 90-97 (2017).
40. Louis, P., Hold, G. L. & Flint, H. J. The gut microbiota, bacterial metabolites and colorectal cancer. Nat. Rev. Microbiol. 12, 661-672 (2014).
41. L. Sears, C. & S. Garrett, W. Microbes, Microbiota and Colon Cancer. Cell Host Microbe 15, 317-328 (2015).
42. Narayanan, V., Peppelenbosch, M. P. & Konstantinov, S. R. Human fecal microbiome-based biomarkers for colorectal cancer. Cancer Prev. Res. (2014). doi:10.1158/1940-6207.CAPR-14-0273
43. Macfarlane, G. T. & Macfarlane, S. Bacteria, Colonic Fermentation, and Gastrointestinal Health. J. AOAC Int. 95, 50-60 (2012).
44. Bauemler, A. J. & Sperandio, V. Interactions between the microbiota and pathogenic bacteria in the gut. Nature 535, 85-93 (2016).
45. Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, 34-1 (2002).
46. Chiu, H. M. et al. Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test. Clin. Gastroenterol. Hepatol. 11, 832-838 (2013).
47. Song, L.-L. & Li, Y.-M. Current noninvasive tests for colorectal cancer screening: An overview of colorectal cancer screening tests. World J. Gastrointest. Oncol. 8, 793 (2016).
48. Bailey, J. R., Aggarwal, A. & Imperiale, T. F. Colorectal Cancer Screening: Stool DNA and Other Noninvasive Modalities. Gut Liver 10, 204-211 (2016).
49. Conlon, M. A. & Bird, A. R. The Impact of Diet and Lifestyle on Gut Microbiota and Human Health. Nutrients 7, 17-44 (2015).
50. Vandeputte, D. et al. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut 65, 57-62 (2015).
51. Davis, S. C., Yadav, J. S., Barrow, S. D. & Robertson, B. K. Gut microbiome diversity influenced more by the Westernized dietary regime than the body mass index as assessed using effect size statistic. Microbiologyopen 6, 1-17 (2017).
52. Yun, Y. et al. Comparative analysis of gut microbiota associated with body mass index in a large Korean cohort. BMC Microbiol. 17, (2017).
53. Rogers, M. A. M. et al. Higher Rates of Clostridium difficile Infection among Smokers. (2012). doi:10.1371/journal.pone.0042091
54. Capurso, G. & Lahner, E. The interaction between smoking, alcohol and the gut microbiome. Best Pract. Res. Clin. Gastroenterol. 31, 579-588 (2017).
55. Baothman, O. A., Zamzami, M. A., Taher, I., Abubaker, J. & Abu-Farha, M. The role of Gut Microbiota in the development of obesity and Diabetes. Lipids Health Dis. 15, (2016).
56. Watt, E. et al. Extending colonic mucosal microbiome analysis-assessment of colonic lavage as a proxy for endoscopic colonic biopsies. Microbiome 4, (2016).
57. Durban, A. et al. Assessing Gut Microbial Diversity from Feces and Rectal Mucosa. Microb. Ecol. 61, 123-133 (2011).
58. Biedermann, L. et al. Smoking Cessation Induces Profound Changes in the Composition of the Intestinal Microbiota in Humans. PLoS One 8, (2013).
59. Kakiyama, G. et al. Modulation of the Fecal Bile Acid Profile by Gut Microbiota in Cirrhosis. J. Hepatol. 58, 949-955 (2013).
60. Rao, R. K., Seth, A. & Sheth, P. Recent Advances in Alcoholic Liver Disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am. J. Physiol. 286, 881-884 (2004).
61. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027-1031 (2006).
62. Schwiertz, A. et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18, 190-195 (2010).
63. Santacruz, A. et al. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity 17, 1906-1915 (2009).
64. Sonnenberg, A., Delco, F. & Inadomi, J. M. Cost-Effectiveness of Colonoscopy in Screening for Colorectal Cancer. Ann. Intern. Med. 133, 573 (2000).
65. McGrath, J. S., Ponich, T. P. & Gregor, J. C. Screening for colorectal cancer: the cost to find an advanced adenoma. Am. J. Gastroenterol. 97, 2902-2907 (2002).
66. Telford, J. J., Levy, A. R., Sambrook, J. C., Zou, D. & Enns, R. A. The cost-effectiveness of screening for colorectal cancer. Can. Med. Assoc. J. 182, 1307-1313 (2010).
67. Wong, M. C., Ching, J. Y., Chan, V. C. & Sung, J. J. The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy. (2015). doi:10.1038/srep13568
68. Garcia, M. et al. False-positive results from colorectal cancer screening in Catalonia (Spain), 2000-2010. J. Med. Screen. 19, 77-82 (2012).
69. Matsuda, K. et al. Bacterial Identification by 16S rRNA Gene PCR-Hybridization as a Supplement to Negative Culture Results. J. Clin. Microbiol. 49, 2031-2034 (2011).
Claims (16)
- 被験体における結腸直腸進行新生物(AN)、進行腺腫(AA)、及び/又は結腸直腸癌(CRC)をスクリーニング、診断、及び/又はモニタリングする便潜血検査(FOBT)の特異度を高める又は偽陽性率を減らす方法であって、
a.前記被験体から単離された糞便試料においてFOBTを実施することと、
ここで、前記FOBTは、前記糞便試料中の潜血の存在の判断を含む;
b.前記被験体から単離された糞便試料において、少なくとも以下の細菌マーカー:
ペプトストレプトコッカス・ストマティス(PTST)、
バクテロイデス・フラジリス(BCTF)、及び、
バクテロイデス・テタイオタオミクロン(BCTT)、
を定量化することと、
を含み、ここで、結腸直腸進行新生物(AN)という前記用語は、CRC及び進行腺腫(AA)を包含する、方法。 - 被験体における結腸直腸進行新生物(AN)、進行腺腫(AA)、及び/又は結腸直腸癌(CRC)をスクリーニング、診断、及び/又はモニタリングする方法であって、
a.前記被験体から単離された糞便試料においてFOBTを実施することと、
ここで、前記FOBTは、前記糞便試料中の潜血の存在の判断を含む;
b.前記被験体から単離された糞便試料において、少なくとも以下の細菌マーカー:
ペプトストレプトコッカス・ストマティス(PTST)、
バクテロイデス・フラジリス(BCTF)、及び、
バクテロイデス・テタイオタオミクロン(BCTT)、
を定量化することと、
を含み、ここで、結腸直腸進行新生物(AN)という前記用語は、CRC及び進行腺腫(AA)を包含する、方法。 - 前記方法は、
c)b)で決定された前記細菌マーカーのレベルから組合せスコアを計算することと、
d)FOBT陽性被験体を、c)で得られた前記組合せスコアに従って、AN、AA、及び/又はCRCを有するとして分類することと、
を更に含む、請求項2に記載のヒト被験体におけるAN、AA、及び/又はCRCをスクリーニング、診断、及び/又はモニタリングする方法。 - c)で計算された前記組合せスコアは、PTST及びBCTFの量に比例し、かつBCTTの量に反比例し、ここで、前記スコアが高いほど、AN、AA、及び/又はCRCを有する可能性が高い、請求項3に記載の方法。
- 工程d)において、前記方法は、前記被験体の試料における前記組合せスコアと、参照値とを比較することを含み、前記参照値に対する前記被験体の試料における前記組合せスコアの増加は、AN、AA、及び/又はCRCの指標である、請求項2~4のいずれか一項に記載の方法。
- 前記方法は、
i.前記糞便試料中のGMLL、PTST、及びBCTTの量と、対応する参照値とを比較すること、
を更に含み、ここで、
ii.前記対応する参照値に対するFOBT陽性被験体の試料におけるGMLL及びPTSTの量の増加、並びにBCTTの量の減少が、AN、AA、及び/又はCRCの指標である、請求項2に記載のヒト被験体におけるAN、AA、及び/又はCRCをスクリーニング、診断、及び/又はモニタリングする方法。 - 前記被験体は、CRCを有することが疑われる被験体、又は無症状の被験体である、請求項1~6のいずれか一項に記載の方法。
- 前記FOBTは、ヒトヘモグロビン(hHb)を定量化する糞便免疫化学検査(FIT)である、請求項1~7のいずれか一項に記載の方法。
- FIT陽性被験体は、糞便1g当たり10μg以上のhHb(FIT50のカットオフ)又は糞便1g当たり20μg以上のhHb(FIT100のカットオフ)のhHbレベルを有し、好ましくは、FIT陽性被験体は、糞便1g当たり10μg以上のhHb(FIT50のカットオフ)のhHbレベルを有する、請求項8に記載の方法。
- 前記方法は、B10(配列番号7)、B46(配列番号8)、B48(配列番号9)、ゲメラ・モルビロルム(GMLL)、ロゼブリア・インテスティナリス(RSBI)、コリンセラ・インテスティナリス(CINT)、フィーカリバクテリウム・プラウスニッツィイ、及び/又はその系統群のいずれか、並びにエシェリキア・コリ(ECO)からなる群より選択される1種以上の細菌マーカーを定量化することを更に含む、請求項1~9のいずれか一項に記載の方法。
- PTST、BCTF、及びBCTT、並びに任意に請求項10の前記細菌マーカーのレベルの決定は、qPCRによって行われ、好ましくは、前記定量化のレベルはCt値として表現される、請求項1~10のいずれか一項に記載の方法。
- PTST、BCTF、及びBCTTのレベル、並びに任意に請求項10の前記細菌マーカーのレベルは、好ましくは真正細菌(EUB)レベルに対する相対的存在量として表現される、請求項1~11のいずれか一項に記載の方法。
- 前記方法は、該方法の結果をデータ担体に格納することを更に含み、好ましくは、前記データ担体は、コンピューター可読媒体である、請求項1~12のいずれか一項に記載の方法。
- 請求項1~13のいずれか一項に規定される通りの方法である、コンピューター実装方法。
- PTST、BCTF、及びBCTTを定量化するのに適したキットであって、以下の試薬:
配列番号24若しくは配列番号25のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド、
配列番号26若しくは配列番号27のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド、及び、
配列番号30若しくは配列番号31のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド、及び、
任意に、真正細菌の定量化に適したオリゴヌクレオチド、好ましくは、配列番号5、配列番号6、配列番号14、若しくは配列番号15のいずれか、又はそれらのいずれかと少なくとも80%の同一性を有する配列を含む又はそれらのみからなるオリゴヌクレオチド、
を含み、
任意に、被験体から単離された糞便試料中の細菌マーカーのレベルを決定する際の前記試薬の使用についての使用説明書を更に含む、キット。 - 請求項1~14のいずれか一項に記載のAN、AA、及び/又はCRCをスクリーニング、診断、及び/又はモニタリングする方法における、請求項15に記載のキットの使用。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP19382186.5 | 2019-03-13 | ||
EP19382186 | 2019-03-13 | ||
EP19382833.2 | 2019-09-26 | ||
EP19382833 | 2019-09-26 | ||
PCT/EP2020/056575 WO2020182922A1 (en) | 2019-03-13 | 2020-03-11 | Improved method for the screening, diagnosis and/or monitoring of colorectal advanced neoplasia, advanced adenoma and/or colorectal cancer |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2022523596A true JP2022523596A (ja) | 2022-04-25 |
Family
ID=69726600
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021553792A Pending JP2022523596A (ja) | 2019-03-13 | 2020-03-11 | 結腸直腸進行新生物、進行腺腫、及び/又は結腸直腸癌をスクリーニング、診断、及び/又はモニタリングする改善された方法 |
Country Status (10)
Country | Link |
---|---|
US (1) | US20220145400A1 (ja) |
EP (1) | EP3938542A1 (ja) |
JP (1) | JP2022523596A (ja) |
KR (1) | KR20210141552A (ja) |
CN (1) | CN114207150A (ja) |
AU (1) | AU2020235239A1 (ja) |
CA (1) | CA3132912A1 (ja) |
IL (1) | IL286255A (ja) |
MX (1) | MX2021011064A (ja) |
WO (1) | WO2020182922A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102513540B1 (ko) * | 2020-11-19 | 2023-03-24 | 고려대학교 산학협력단 | 대장점막의 장내미생물총분석을 이용한 고위험성대장선종, 진행성 결장암 궤양성 대장염 및 정상대조군의 감별 진단 방법 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2003245465A1 (en) | 2002-02-13 | 2003-09-04 | Medimolecular Pty. Ltd. | Method of isolating nucleic acids from stool samples |
WO2012177639A2 (en) * | 2011-06-22 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Bioprocessing and bioproduction using avian cell lines |
EP2915884B1 (en) | 2014-03-03 | 2017-12-06 | Fundacio Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta | Method for diagnosing colorectal cancer from a human feces sample by quantitive PCR |
EP2955232B1 (en) * | 2014-06-12 | 2017-08-23 | Peer Bork | Method for diagnosing adenomas and/or colorectal cancer (CRC) based on analyzing the gut microbiome |
CN107208141B (zh) * | 2015-01-13 | 2021-01-12 | 深圳华大基因科技有限公司 | 用于结直肠癌相关疾病的生物标志物 |
CA2981508A1 (en) * | 2015-04-01 | 2016-10-06 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating duchenne muscular dystrophy and becker muscular dystrophy |
EP3130680A1 (en) | 2015-08-11 | 2017-02-15 | Universitat de Girona | Method for the detection, follow up and/or classification of intestinal diseases |
WO2018036503A1 (en) * | 2016-08-25 | 2018-03-01 | The Chinese University Of Hong Kong | Fecal bacterial markers for colorectal cancer |
-
2020
- 2020-03-11 CN CN202080036174.7A patent/CN114207150A/zh active Pending
- 2020-03-11 MX MX2021011064A patent/MX2021011064A/es unknown
- 2020-03-11 JP JP2021553792A patent/JP2022523596A/ja active Pending
- 2020-03-11 AU AU2020235239A patent/AU2020235239A1/en active Pending
- 2020-03-11 KR KR1020217033042A patent/KR20210141552A/ko unknown
- 2020-03-11 US US17/438,173 patent/US20220145400A1/en active Pending
- 2020-03-11 WO PCT/EP2020/056575 patent/WO2020182922A1/en unknown
- 2020-03-11 EP EP20708152.2A patent/EP3938542A1/en active Pending
- 2020-03-11 CA CA3132912A patent/CA3132912A1/en active Pending
-
2021
- 2021-09-09 IL IL286255A patent/IL286255A/en unknown
Also Published As
Publication number | Publication date |
---|---|
KR20210141552A (ko) | 2021-11-23 |
MX2021011064A (es) | 2021-10-13 |
IL286255A (en) | 2021-10-31 |
EP3938542A1 (en) | 2022-01-19 |
CN114207150A (zh) | 2022-03-18 |
WO2020182922A1 (en) | 2020-09-17 |
AU2020235239A1 (en) | 2021-10-07 |
US20220145400A1 (en) | 2022-05-12 |
CA3132912A1 (en) | 2020-09-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Eklöf et al. | Cancer‐associated fecal microbial markers in colorectal cancer detection | |
Mei et al. | Characterization of the duodenal bacterial microbiota in patients with pancreatic head cancer vs. healthy controls | |
Liguori et al. | Fungal dysbiosis in mucosa-associated microbiota of Crohn’s disease patients | |
Kohi et al. | Alterations in the duodenal fluid microbiome of patients with pancreatic cancer | |
KR102354660B1 (ko) | 정량 pcr, 프라이머 및 키트에 의한 인간 대변 시료로부터의 대장암의 진단 방법 | |
US20220307075A1 (en) | Method for the quantification of faecalibacterium prausnitzii phylogroup i and/or phylogroup ii members and the use thereof as biomarkers | |
Chipollini et al. | Characterization of urinary microbiome in patients with bladder cancer: Results from a single-institution, feasibility study | |
Cabanero et al. | Circulating tumour DNA in EGFR-mutant non-small-cell lung cancer | |
Chen et al. | Berberine inhibits intestinal carcinogenesis by suppressing intestinal pro-inflammatory genes and oncogenic factors through modulating gut microbiota | |
Ito et al. | Utility of liquid biopsy by improved PNA-LNA PCR clamp method for detecting EGFR mutation at initial diagnosis of non–small-cell lung cancer: observational study of 190 consecutive cases in clinical practice | |
JP2022523596A (ja) | 結腸直腸進行新生物、進行腺腫、及び/又は結腸直腸癌をスクリーニング、診断、及び/又はモニタリングする改善された方法 | |
WO2016119190A1 (en) | Biomarkers for colorectal cancer related diseases | |
EP2909335B1 (en) | Prognostic of diet impact on obesity-related co-morbidities | |
WO2016119191A1 (en) | Biomarkers for colorectal cancer related diseases | |
Li et al. | Association of CFH polymorphism with susceptibility to sepsis caused by Pseudomonas aeruginosa in Chinese Han populations: A multi-center study | |
WO2023080154A1 (ja) | 有害事象リスクの判定方法 | |
Zuraik et al. | Effect of chemotherapy on Fusobacterium nucleatum abundance in colorectal cancer patients: A study on relapsing patients | |
Ugai et al. | Clinicopathological, molecular, and prognostic features of colorectal carcinomas with KRAS c. 34G> T (p. G12C) mutation | |
Zhang et al. | Dysbiosis of the Fecal Microbiota in Patients with Cholangiocarcinoma: A Pilot Study | |
del Rey-Pineda et al. | Serum PCR in diagnosis of neonatal sepsis caused by bacteria and enteroviruses. | |
Al Abri et al. | IDH1 and IDH2 Gene Mutations in Omani Patients with Acute Myeloid Leukemia: Prognostic Significance and Clinic-pathologic Features | |
Yu et al. | PS02. 235: POOR ORAL HEALTH INCREASES RISK OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA: THE FOLLOW-UP STUDY OF THE LINXIAN NUTRITION INTERVENTION TRIAL. | |
Merisescu et al. | TAXONOMY OF THE UPDATED DEFINITION AND STAGING CRITERIA OF BACTERIAL SEPSIS. | |
WO2018202666A1 (en) | Cpg-site methylation markers in colorectal cancer | |
Gupta | Understanding the role of infections in the pathogenesis of inflammatory bowel disease, and improving the quality and safety of treatment |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20211105 |
|
RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20211102 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20230310 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20240216 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240220 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240520 |